BACKGROUND: The inner surface and capsule of joints are lined by a delicate vascular connective tissue known as the synovial membrane. In rheumatoid arthritis and related conditions, the membrane may become massively inflamed and thickened. OBJECTIVE: The objectives of this study are to characterize these tissues in terms of the molecular mediators involved in generating the pathologic change. Over the past 3 years, we have been particularly interested in characterizing type 1 and type 2 cytokines during the earliest stages of synovitis (i.e., early synovitis). In a study of more than 200 synovial specimens from patients with new onset rheumatoid, reactive and undifferentiated arthritis, we demonstrated that cytokine profiles are skewed toward proinflammatory macrophage-derived and Th1 type cytokines such as TNF-alpha, IL-beta, IL-12 and IL-15. Interestingly, IL-2 and gamma interferon were more abundant in reactive arthritis relative to rheumatoid arthritis. IL-10 was also abundant in all patient groups and represented the major anti-inflammatory cytokine. IL-4 and IL-13 were rare. Our most recent studies have focused on a subgroup of patients with Chlamydia-associated arthritis who were not treated with second-line drugs or corticosteroids. RESULTS: We completed the laboratory analyses in these patients. All of the Chlamydia-associated arthritis patients had very high levels of both gamma interferon and IL-10 relative to our control groups with other diagnoses or normal control synovial tissues. We have speculated that the high levels of both a type 1 and type 2 cytokine may favor persistence of the organism in the joints. A manuscript has been submitted for publication. CONCLUSIONS: Inflammatory synovitis, in its earliest stages, represents a very heterogeneous group of clinical disorders. They appear to have variable genetic influences, environmental triggers, pathogenic mechanisms and responses to therapy. Chlamydia-associated early arthritis appears to be very common. Our studies provide potential insights into factors that may influence the chronicity of this condition and may ultimately lead to new approaches to diagnosis and therapy. These patients provide an excellent contrasting control group for patients with other forms of arthritis, such as rheumatoid arthritis.